Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT28QL7H)

• DOT Name: Thialysine N-epsilon-acetyltransferase (SAT2)
• Synonyms: EC 2.3.1.-; Diamine acetyltransferase 2; EC 2.3.1.57; Spermidine/spermine N(1)-acetyltransferase 2; SSAT-2
• Gene Name: SAT2
• Related Disease:
  Adenocarcinoma
  Adenoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Hepatocellular carcinoma
  Intestinal neoplasm
  Male infertility
  Neoplasm
  Prostate adenocarcinoma
  Stomach cancer
  facioscapulohumeral muscular dystrophy
  Frontometaphyseal dysplasia 1
  Gastric cancer
  Melanoma
  Childhood kidney Wilms tumor
  Invasive ductal breast carcinoma
  Wilms tumor
• UniProt ID: SAT2_HUMAN
• PDB ID: 2BEI; 2Q4V
• EC Number: 2.3.1.-; 2.3.1.57
• Pfam ID: PF00583
• Sequence:
  MASVRIREAKEGDCGDILRLIRELAEFEKLSDQVKISEEALRADGFGDNPFYHCLVAEIL
  PAPGKLLGPCVVGYGIYYFIYSTWKGRTIYLEDIYVMPEYRGQGIGSKIIKKVAEVALDK
  GCSQFRLAVLDWNQRAMDLYKALGAQDLTEAEGWHFFCFQGEATRKLAGK
• Function: Catalyzes the N-acetylation of the amino acid thialysine (S-(2-aminoethyl)-L-cysteine), a L-lysine analog with the 4-methylene group substituted with a sulfur. May also catalyze acetylation of polyamines, such as norspermidine, spermidine or spermine. However, ability to acetylate polyamines is weak, suggesting that it does not act as a diamine acetyltransferase in vivo.
• Tissue Specificity: Widely expressed . Under physiological conditions, SSAT2 is expressed at lower level that SSAT1 (SSAT). Many tissues express only SSAT1, several tissues express both SSAT1 and SSAT2, and bone, cervix, ovary and pineal gland expressed only SSAT2 .
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
  Ferroptosis (hsa04216)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Posttranslational Modification	[1]
Adenoma	DIS78ZEV	Strong	Posttranslational Modification	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[7]
Intestinal neoplasm	DISK0GUH	Strong	Altered Expression	[4]
Male infertility	DISY3YZZ	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[10]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
facioscapulohumeral muscular dystrophy	DISSE0H0	moderate	Genetic Variation	[12]
Frontometaphyseal dysplasia 1	DIS2MB3L	moderate	Genetic Variation	[12]
Gastric cancer	DISXGOUK	moderate	Biomarker	[11]
Melanoma	DIS1RRCY	moderate	Altered Expression	[13]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[14]
Invasive ductal breast carcinoma	DIS43J58	Limited	Biomarker	[15]
Wilms tumor	DISB6T16	Limited	Biomarker	[14]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[20]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[21]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[22]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Thialysine N-epsilon-acetyltransferase (SAT2).	[27]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Thialysine N-epsilon-acetyltransferase (SAT2).	[24]

References

• [1] DNA hypomethylation is prevalent even in low-grade breast cancers.Cancer Biol Ther. 2004 Dec;3(12):1225-31. doi: 10.4161/cbt.3.12.1222. Epub 2004 Dec 9.
• [2] DNA methylation changes in ex-adenoma carcinoma of the large intestine.Virchows Arch. 2010 Oct;457(4):433-41. doi: 10.1007/s00428-010-0958-9. Epub 2010 Aug 14.
• [3] DNA methylation as a promising landscape: A simple blood test for breast cancer prediction.Tumour Biol. 2015 Jul;36(7):4905-12. doi: 10.1007/s13277-015-3567-z. Epub 2015 Jun 16.
• [4] Evaluation of SAT-1, SAT-2 and GalNAcT-1 mRNA in colon cancer by real-time PCR.Mol Cell Biochem. 2007 Apr;298(1-2):59-68. doi: 10.1007/s11010-006-9350-0. Epub 2006 Nov 21.
• [5] Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer.Epigenetics. 2013 Jul;8(7):748-55. doi: 10.4161/epi.25178. Epub 2013 Jun 17.
• [6] Adenovirus-mediated expression of spermidine/spermine N1-acetyltransferase gene induces S-phase arrest in human colorectal cancer cells.Oncol Rep. 2008 Nov;20(5):1229-35.
• [7] Global DNA methylation in a population with aflatoxin B1 exposure.Epigenetics. 2013 Sep;8(9):962-9. doi: 10.4161/epi.25696. Epub 2013 Jul 18.
• [8] Increased Sat2 expression is associated with busulfan-induced testicular Sertoli cell injury.Toxicol In Vitro. 2017 Sep;43:47-57. doi: 10.1016/j.tiv.2017.05.023. Epub 2017 Jun 1.
• [9] Methylation status of normal background mucosa is correlated with occurrence and development of neoplasia in the distal colon.Hum Pathol. 2010 Jan;41(1):38-47. doi: 10.1016/j.humpath.2009.06.002. Epub 2009 Sep 5.
• [10] Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm.Virchows Arch. 2009 Jan;454(1):17-23. doi: 10.1007/s00428-008-0706-6. Epub 2008 Dec 2.
• [11] Hypomethylation of repetitive elements in blood leukocyte DNA and risk of gastric lesions in a Chinese population.Cancer Epidemiol. 2016 Apr;41:122-8. doi: 10.1016/j.canep.2016.02.004. Epub 2016 Mar 1.
• [12] Generation of monoclonal antibodies against foot-and-mouth disease virus SAT 2 and the development of a lateral flow strip test for virus detection.Transbound Emerg Dis. 2019 May;66(3):1158-1166. doi: 10.1111/tbed.13076. Epub 2018 Dec 10.
• [13] Cancer-linked satellite 2 DNA hypomethylation does not regulate Sat2 non-coding RNA expression and is initiated by heat shock pathway activation.Epigenetics. 2012 Aug;7(8):903-13. doi: 10.4161/epi.21107. Epub 2012 Jun 22.
• [14] Global demethylation in loss of imprinting subtype of Wilms tumor.Genes Chromosomes Cancer. 2013 Feb;52(2):174-84. doi: 10.1002/gcc.22017. Epub 2012 Oct 17.
• [15] Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients.Anticancer Res. 2010 Jul;30(7):2489-96.
• [16] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [17] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [18] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [19] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [20] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [21] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [22] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [23] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [24] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [25] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.